Do All Antidepressants Cause QT Prolongation? Medication-Induced QT-Interval Prolongation and Torsades de Pointes. The single most common cause of the withdrawal or restriction of the use of marketed drugs has been QT-interval prolongation associated with polymorphic ventricular tachycardia, or torsade de point. Drugs that prolong the QT interval Prolongation of the QT interval can lead to a life threatening ventricular arrhythmia known as torsades de pointes which can result in sudden cardiac death. Further data • Investigators measured: - The plasma concentrations of QT drugs achieved during usual US Pharm. Torsades de pointes (TdP) is an ECG manifestation characterized by a form of ventricular tachycardia with a spiral appearance and complexes that first look positive and then negative. The single most common cause of the withdrawal or restriction of the use of marketed drugs has been QT-interval prolongation associated with polymorphic ventricular tachycardia, or torsade de . Avoid drug interactions, particularly multiple drugs associated with QTc prolongation. QT prolongation is an established side effect of anti-arrhythmic medicines, but can also be caused by a wide range of non-cardiac medicines, including antibiotics, antihistamines, opioid analgesics and complementary medicines. the uk medicines and healthcare products regulatory agency (mhra) has released warnings relating to drug-induced qt prolongation for many commonly used drugs, such as citalopram, domperidone, ondansetron and quinine. Prolongation of the QT interval is a serious electrocardiogram finding because of its association with torsades de pointes and sudden cardiac death.1 Both congenital and acquired factors can lead to abnormal lengthening of the QT interval. b Torsadogenic potential is divided into four categories as characterized in a previous publication 1: high = drugs that are potent blockers of currents The QT interval represents the summation of cardiac action potentials. The review discusses safety implications of drugs found to shorten the QT/QTc interval. Physicians need to know: • What drugs cause QT prolongation. So, here is a mnemonic for drugs causing QT prolongation. TCAs act on both sodium and IKr channels, which can potentially lead to electrophysiologic changes, such as widening of the QRS complex and QT interval prolongation. o Amiodarone. It prolongs QTc in a dose-dependent manner with a rapid onset and return to near baseline within 2 to 6 hours. Potential risk and degree of QT prolongation associated with the drug The UK Medicines and Healthcare products Regulatory Agency (MHRA) has released warnings relating to drug-induced QT pro- Some drugs can cause QT prolongation (drug induced QT prolongation), and it have to be strictly controlled for patient safety. Certain drugs, including some anesthetics, are known to contribute to QT prolongation. Because of its multiple actions, amiodarone causes QT prolongation but TdP is . For some drugs, such as sotalol, amisulpride and citalopram or escitalopram, there is a lot of information on the risk of QT prolongation and torsades de pointes (Fig. Click on a drug and see if the FDA-approved label recommends ECG monitoring. UPDATED JAN 2016 QT prolonging drugs lists can fit these three criteria: Possible Risk of QT prolongation/TdP Substantial evidence supports the conclusion that these drugs can cause QT prolongation BUT there is insufficient evidence at this time that these drugs, when used as directed in official labeling, are associated with a risk of causing TdP. There are three mechanisms by which drugs can interact and increase the risk of . Further information on QT prolongation can be found in the Prescriber Update article 'Drug-induced QT prolongation and Torsades de Pointes — the facts' 2. Drugs associated with QT prolongation include those drugs that predictably prolong the QT interval. December 2010. Medication-induced QT prolongation was first recognized with the use of quinidine in the 1920s. Drastic changes in electrolyte concentrations should be avoided in patients with congenital long QT syndrome along with these drugs. Antipsychotic drugs (AD) are effective and frequently prescribed to more females than males. Interactions Antidepressants: Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have also been associated with QT prolongation and TdP. Many medications increase the risk of QT prolongation, a dangerous type of irregular heart rhythm (arrhythmia). QT-Prolonging Medications. Although hundreds of ion channel gene mutations have been identified as associated with . This review focuses on the mechanism of drug-induced QT prolongation, risk factors for TdP, culprit drugs, prevention and monitoring of prolonged drug-induced QT prolongation and . Overview of Long QT Syndrome and Torsades de Pointes. • Drug induced QT prolongation is usually dose related • Roughly for every 10 msec increase in QTc, there is a 5% increase in the risk of TdP *2011 AHA/ACC scientific statement . It is important to remember that QT prolongation can result from multiple factors,either multiple drugs or a com-bination of drugs and non-drug factors [5]. 1 Both phenothiazines and butyrophenones are known to cause QTc prolongation because of their inhibition of IKr potassium efflux channels and are similarly limited by extrapyramidal side effects (2, 6). found that methadone was the leading cause of TdP among 2735 patients with prolonged QT interval who were taking prescription drugs. Drugs can cause prolongation of the QT interval, alone or in combination, potentially leading to fatal arrhythmias such as torsades de pointes. These patients have abnormally long QT intervals due to one or more mutations in genes that encode the structure of cardiac ion channels. Advertisement. The plasma concentrations of the drug fall rapidly following intravenous infusion, and it has no known active metabolites, 11 making ibutilide an excellent probe to study differences in drug-induced QT prolongation. When TdP occurs it is imperative to identify the potential offending agent . 3) The degree of the potential risk and degree of QTc prolongation that can be induced by the drug. What Drugs Cause QT Prolongation? Data on drugs causing mean increases of around 5 milliseconds and less than 20 milliseconds are inconclusive, and some drugs causing this have been associated with proarrhythmic risk. drugs that prolong the qt interval drugs category antihistamines anti-i nfectives antineoplastics anti arrhythmics antilipemic agents calcium channel blockers diuretics gastrointestinal agents hormones antidepressants antipsychotic astemizole, terfenadine amantadine, clarithromycin, chloroquine, erythromycin, grepafloxacin, moxifloxacin, … Initial post October 29, 2010 (Latest revision: Sept 28, 2019) Drug-induced long QT syndrome (diLQTS) and torsades de pointes (TdP) are important clinical entities that all physicians and health-care providers should recognize and be able to manage because they can occur as a side effect of over 200 medications and, in some cases, can be fatal. arrhythmias. QT Drugs Lists: This portal includes QTdrugs.org, a list of drugs categorized by their potential to cause QT prolongation and/or torsades de pointes (TdP). formula. It is known that some drugs associated with QT c prolongation Prolonged use (>14 days) of any PPI should be discouraged in this special population because of their inherent high risk of TdP. •Even though drug-induced TdP is a relatively rare event, sudden cardiac death and TdP due to drug-induced QT interval prolongation are top reasons that prompt the U.S. Food and Drug Administration (FDA) from removing drugs from the U.S. market. The QT interval is a section of the electrocardiogram (ECG or EKG), and having a QT interval that is too long can be dangerous. Drug-induced QT prolongation is defined as a QTc of 500 ms or greater or an increase of 60 ms or greater in the QT interval compared with the premedication baseline interval. Pantoprazole has also been added to the list of "Drugs to Avoid in Patients with congenital Long QT. A safe drug in one patient may be potentially harmful in another. However, it has been observed that there are more drugs that have this side effect such as some antihistamines, antibiotics, antivirals, antifungals, antiemetics, neuroleptics, antidepressants, among others. Increase monitoring frequency in patients with risk factors for QTc prolongation [see Warnings and Precautions (5.1)]. Z Gerontol Geriatr . It blocks sodium, potassium, and calcium channels, as well as alpha and beta-adrenergic receptors. Six types of congenital long QT syndrome (LQT1-LQT6) have been described, each involving mutations in genes encoding potassium or sodium transmembrane . It blocks sodium, potassium, and calcium channels, as well as alpha and beta-adrenergic receptors. Drug Induced QT Prolongation ICU patients at high risk for drug-drug interactions 18.6% of patients on >1 QT-prolonging drug had increased mortality Many patients exposed to QT-prolonging agents in ICU Increased drastically in cardiovascular ICU True prevalence difficult to assess Arrhythmias typically fatal outside the hospital Amiodarone works in many ways. • How to identify patients at particular risk. Torsades de pointes; drug induced QT prolongation; antiarrhythmics; antihistamines; antimicrobials; antidepressants; In 1966, Francois Dessertenne described a specific electrocardiographic form of polymorphic ventricular tachycardia, which he termed "torsades de pointes" (TdP). Because of its multiple actions, amiodarone causes QT prolongation but TdP is . Medication-induced QT prolongation was first recognized with the use of quinidine in the 1920s. o Class III antiarrhythmic drugs are potassium channel blockers that cause QT prolongation and are associated with TdP. The list of drugs that cause QT prolongation continues to grow, and an updated list of specific drugs that prolong the QT interval can be found at www.qtdrugs.org. 2016 Nov 22. Abnormality in repolarization of the heart; It could increase risk of life-threatening arrhythmia, Torsades de point. This cardiac disturbance carries a 10% risk of sudden cardiac death due to the malignant arrhythmia, Torsades de Pointes. cisapride and terfenadine) have been withdrawn . Physicians, other healthcare providers and patients need to be aware of drug-induced LQTS. However, a paradigm shift is taking place in the preclinical and clinical evaluation of drug-induced QT . Several drugs (e.g. Epidemiologic data and case-control studies indicate an in … (e.g. Secondly, there are a number of drugs that have . They are all used to treat arrhythmias and include quinidine, procainamide, amiodarone, sotalol, and dofetilide (referred to as Class I drugs). Associations are based on the strength of evidence that supports whether QT prolongation can occur. Prescribers are advised to consider the possibility of drug-induced QT prolongation or Torsades de Pointes (TdP) in patients presenting with new onset syncope, palpitations, seizures or resuscitated cardiac arrest. Drug Induced QT Prolongation ICU patients at high risk for drug-drug interactions 18.6% of patients on >1 QT-prolonging drug had increased mortality Many patients exposed to QT-prolonging agents in ICU Increased drastically in cardiovascular ICU True prevalence difficult to assess Arrhythmias typically fatal outside the hospital warnings relating to drug-induced QT prolongation for three commonly used drugs - citalopram, domperidone and ondansetron.1,2,3 Extra vigilance is required by healthcare professionals to be alert to the risk of drug induced QT prolongation and drug interactions. When prescribing drugs that prolong the QT interval, the balance of benefit versus harm should always be considered. antiarrhythmic drug states that drugs causing an increase in mean QT/QTc interval of around 5 milliseconds or less do not appear to cause torsade de pointes. 2 Drug-induced QT prolongation is thought to be caused by the inhibition of the delayed potassium rectifier current IKr (rapid) by specific drugs. There are three mechanisms by which drugs can interact and . Mnemonics make this task easy. 29-32 from a practical perspective, data are inconclusive with regard to arrhythmic risk for drugs that increase the qtc interval … 2011;36(2):HS-2-HS-8. Use the lowest possible dose and/or administer at a slow rate. Hepatic insufficiency in seropositive patients on antiretrovirals may also increase the risk of QT interval prolongation. It summarizes the evidence that increases in repolarization heterogeneity are likely more important for arrhythmia induction and maintenance than the absolute changes in the QT/QTc duration. QT Prolongation Associated with Drug Interactions. decision to commence a QT-prolonging drug should be made collaboratively with the patient, and the potential impact should be clearly communicated. Some research suggests that these medications. AD may cause serious cardiovascular side-effects, including prolonged QT interval, eventually leading to torsades de pointes (TdP) and sudden death. The single most common cause of the withdrawal or restriction of the use of marketed drugs has been QT-interval prolongation associated with polymorphic ventricular tachycardia, or torsade de point. Drug-induced QT prolongation may also have a genetic background, consisting of the predisposition of an ion channel to abnormal kinetics caused by gene mutation or polymorphism. Among the best-known medications that prolong the QT interval are antiarrhythmics. Torsades de pointes (TdP) is an ECG manifestation characterized by a form of ventricular tachycardia with a spiral appearance and complexes that first look positive and then negative. Diuretics are one class of drugs that may cause QT prolongation. Conclusion: If a person requires diuretics, a doctor may prescribe potassium-sparing diuretics. Drugs Causing QT Prolongation Ed Burns Feb 4, 2021 Home ECG Library Return to ECG Library Homepage Antipsychotics Chlorpromazine Haloperidol Droperidol Quetiapine Olanzapine Amisulpride Thioridazine Type IA antiarrhythmics Quinidine Procainamide Disopyramide Type IC antiarrhythmics Flecainide Encainide Class III antiarrhythmics Sotalol Amiodarone So, here is a mnemonic for drugs causing QT prolongation. Prevention of Drug-Induced QTc Prolongation: Address modifiable risk factors: Limit the use of QTc prolonging drugs in patients with known risk factors.